GABAergic Interneurons at Supraspinal and Spinal Levels Differentially Modulate the Antinociceptive Effect of Nitrous Oxide in Fischer Rats
| Autor: | Ryo Orii, Sunil Halder, Mariangela Giombini, Mervyn Maze, Masahiko Fujinaga, Yoko Ohashi |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
Nervous system Central nervous system Nitrous Oxide Pharmacology GABA Antagonists chemistry.chemical_compound Interneurons medicine Animals Injections Spinal gamma-Aminobutyric Acid Pain Postoperative Muscimol business.industry Brain Analgesics Non-Narcotic GABA receptor antagonist Spinal cord Rats Inbred F344 Rats Anesthesiology and Pain Medicine medicine.anatomical_structure Nociception Spinal Cord chemistry Gabazine GABAergic business Neuroscience medicine.drug |
| Zdroj: | Anesthesiology. 98:1223-1230 |
| ISSN: | 0003-3022 |
| DOI: | 10.1097/00000542-200305000-00026 |
| Popis: | Background The study hypothesizes that nitrous oxide (N(2)O) releases opioid peptide in the brain stem, which results in inhibition of gamma-aminobutyric acid-mediated (GABAergic) neurons that tonically inhibit the descending noradrenergic inhibitory neurons (DNIN), resulting in activation of DNIN. In the spinal cord, activation of DNIN leads to the release of norepinephrine, which inhibits nociceptive processing through direct activation of alpha2 adrenoceptor and indirect activation of GABAergic neurons through alpha1 adrenoceptor. Arising from this hypothesis, it follows that GABAergic neurons will modulate the antinociceptive effect of N(2)O in diametrically opposite directions at supraspinal and spinal levels. The authors have tested this tenet and further examined the effect of midazolam, a GABA-mimetic agent, on N(2)O-induced antinociceptive effect. Methods Adult male Fischer rats were administered muscimol (GABA(A) receptor agonist) intracerebroventricularly (icv), gabazine (GABA(A) receptor antagonist) intrathecally (intrathecal), or midazolam intraperitoneally (intraperitoneal). Fifteen minutes later, they were exposed to air or 75% N(2)O and were subjected to the plantar test after 30 min of gas exposure. In some animals administered with midazolam, gas exposure was continued for 90 min, and the brain and spinal cord were examined immunohistochemically. Results The N(2)O-induced antinociceptive effect, which was attenuated by icv muscimol, intrathecal gabazine, and intraperitoneal midazolam. Midazolam inhibited N(2)O-induced c-Fos expression (a marker of neuronal activation) in the pontine A7 and spinal cord. Conclusions The GABAergic neurons modulate the antinociceptive effect of N(2)O in opposite directions at supraspinal and spinal levels. The pronociceptive effects of enhancement at the supraspinal GABAergic site predominate in response to systemically administered midazolam. |
| Databáze: | OpenAIRE |
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